There are a number of assays and sensors for the detection of the presence and/or concentration of specific substances in fluids and gases. Many of these rely on specific ligand/antiligand reactions as the mechanism of detection. That is, pairs of substances (i.e. the binding pairs or ligand/antiligands) are known to bind to each other, while binding little or not at all to other substances. This has been the focus of a number of techniques that utilize these binding pairs for the detection of the complexes. These generally are done by labeling one component of the complex in some way, so as to make the entire complex detectable, using, for example, radioisotopes, fluorescent and other optically active molecules, enzymes, etc.
Other assays rely on electronic signals for detection. Of particular interest are biosensors. At least two types of biosensors are known; enzyme-based or metabolic biosensors and binding or bioaffinity sensors. See for example U.S. Pat. Nos. 4,713,347; 5,192,507; 4,920,047; 3,873,267; and references disclosed therein. While some of these known sensors use alternating current (AC) techniques, these techniques are generally limited to the detection of differences in bulk (or dielectric) impedance, and rely on the use of mediators in solution to shuttle the charge to the electrode.
Recently, there have been several preliminary reports on the use of very short connections between a binding ligand and the electrode, for direct detection, i.e. without the use of mediators. See Lötzbeyer et al., Bioelectrochemistry and Bioenergetics 42:1-6 (1997); Dong et al., Bioelectrochemistry and Bioenergetics 42:7-13 (1997).
In addition, there are a number of reports of self-assembled monolayers of conjugated oligomers on surfaces such as gold. See for example Cygan et al., J. Am. Chem. Soc. 120:2721 (1998)
In addition, Charych et al. report on the direct colormetric detection of a receptor-ligand interaction using a bilayer assembly (Science 261:585 (1993).
PCT applications WO 95/15971, PCT/US96/09769, PCT/US97/09739, WO96/40712 and PCT/US97/20014 describe novel compositions comprising nucleic acids containing electron transfer moieties, including electrodes, which allow for novel detection methods of nucleic acid hybridization.
In addition, there are a number of sensors that rely on the use of particles, including magnetic particles, particularly for electrochemiluminescence detection. See U.S. Pat. Nos. 5,746,974; 5,770,459; 5,779,976; 4,731,337; 4,115,535; 4,777,145; 4,945,045; 4,978,610; 5,705,402; 4,910,148; 5,512,439; 5,585,241; and 5,609,907; and WO 90/14891; WO 90/05301; WO 92/14139; and WO 90/06044.
Finally, there are reports that bring particles together using nucleic acids for archetectural reasons. See Mirkin et al., Nature 382:607 (1996); Mirkin et al., Science 277:1078 (1997); Storhoff et al., J. Am. Chem. Soc. 120:1959 (1998); and WO 98/10289.